Unexpected diversity of cnidarian integrins: expression during coral gastrulation
- Brent A Knack†1,
- Akira Iguchi†1,
- Chuya Shinzato1,
- David C Hayward2,
- Eldon E Ball2Email author and
- David J Miller1Email author
© Knack et al; licensee BioMed Central Ltd. 2008
Received: 26 October 2007
Accepted: 09 May 2008
Published: 09 May 2008
Adhesion mediated through the integrin family of cell surface receptors is central to early development throughout the Metazoa, playing key roles in cell-extra cellular matrix adhesion and modulation of cadherin activity during the convergence and extension movements of gastrulation. It has been suggested that Caenorhabditis elegans, which has a single β and two α integrins, might reflect the ancestral integrin complement. Investigation of the integrin repertoire of anthozoan cnidarians such as the coral Acropora millepora is required to test this hypothesis and may provide insights into the original roles of these molecules.
Two novel integrins were identified in Acropora. AmItgα1 shows features characteristic of α integrins lacking an I-domain, but phylogenetic analysis gives no clear indication of its likely binding specificity. AmItgβ2 lacks consensus cysteine residues at positions 8 and 9, but is otherwise a typical β integrin. In situ hybridization revealed that AmItgα1, AmItgβ1, and AmItgβ2 are expressed in the presumptive endoderm during gastrulation. A second anthozoan, the sea anemone Nematostella vectensis, has at least four β integrins, two resembling AmItgβ1 and two like AmItgβ2, and at least three α integrins, based on its genomic sequence.
In two respects, the cnidarian data do not fit expectations. First, the cnidarian integrin repertoire is more complex than predicted: at least two βs in Acropora, and at least three αs and four βs in Nematostella. Second, whereas the bilaterian αs resolve into well-supported groups corresponding to those specific for RGD-containing or laminin-type ligands, the known cnidarian αs are distinct from these. During early development in Acropora, the expression patterns of the three known integrins parallel those of amphibian and echinoderm integrins.
Integrins are a large family of cell surface transmembrane receptors known only from metazoans, which function in intracellular signalling as well as cell-cell and cell-extracellular matrix (ECM) adhesion . As the main mediators of cell-ECM interactions they are key players in early development  functioning in gastrulation by rapid modulation of their own adhesion between low and high affinity states and by modulating the activities of adhesion molecules (e.g. cadherins) in cell layers undergoing convergence and extension .
Integrins function as αβ heterodimers with several subunits of each type being present in most animals. Analyses of the whole genome sequence of Caenorhabditis elegans [4, 5] indicate that it has a single β subunit of the β1 type that is capable of associating with two α subunits, which confer specificity for either laminin- or RGD-containing ligands, and it has been suggested that this may reflect the ancestral state. Drosophila melanogaster has five α and two β subunits  and mammals, eighteen α and eight β integrin subunits . In each case, however, integrin subunits above and beyond likely orthologs of the two αs and one β of Caenorhabditis are clearly lineage-specific. "Lower" animals are of particular significance in terms of understanding the ancestral state, but have not been extensively studied. Both α and β integrin subunits have been identified in sponges [7–9], and cnidarians [7, 10, 11], but the extent of integrin diversity and the range of functions of these molecules in "lower" animals are unknown.
Anthozoan cnidarians such as the coral Acropora millepora and the sea anemone Nematostella vectensis appear to have retained much of the genetic complexity of the metazoan common ancestor [12, 13]; hence these animals are likely to be highly informative with respect to the ancestral integrin complement and may provide insights into the original roles of these molecules. Known cnidarian integrins include a β integrin from Acropora millepora  and single α and β subunits (IntA and IntB) from the hydrozoan jellyfish Podocoryne carnea . Here we report the characterisation of novel β and α integrins from Acropora. The known Acropora integrins are expressed during gastrulation in patterns like those seen at the corresponding stages of echinoderm and amphibian development. However, we know from morphological observation [14, 15] that Acropora gastrulation is not a simple epithelial to mesenchymal transition in which the expressing cells lose their adhesivity and invaginate. Instead, in Acropora it is clear that changing cell shape also plays a major role. Two further implications of this work are that the cnidarian integrin complement is significantly more complex than was predicted, and that functional diversification of α integrins may have occurred independently in Cnidaria and Bilateria.
Identification of novel integrins
Three unigenes encoding integrin subunits were identified during an ongoing EST analysis of Acropora millepora [13, 16]. One of these corresponds to the previously known Acropora integrin β Cn1 ; to simplify comparative analyses, this integrin is henceforth referred to as AmItgβ1. Complete sequences were determined for cDNA clones corresponding to the other two integrin unigenes; comparative analyses indicated that an EST clone corresponding to a second β subunit (AmItgβ2) encodes a full length protein of 771 amino acids, whilst an α integrin EST clone lacked the 5' end of the open reading frame. To complete the 1021 amino acid integrin α coding sequence, overlapping clones were isolated from a cDNA library, enabling the determination of the complete open reading frame for a molecule designated AmItgα1. These sequences have been submitted to GenBank under the following accession numbers: EU239371 (AmItgα1) and EU239372 (AmItgβ2).
AmItgβ2 is a possible coral ortholog of a known jellyfish integrin β
AmItgα1 is a cnidarian integrin resembling the vertebrate α4/9-type
Phylogenetic analyses of the novel integrin sequences
To better understand relationships between the Acropora sequences and the major integrin types of higher animals, maximum likelihood (ML) phylogenetic analyses were undertaken using MolPhy version 2.3 . Integrin phylogenetics is complicated by high levels of primary sequence divergence and homoplasy, leading to difficulties in unambiguous alignment of sequences. The analyses presented here are therefore based on extensively edited alignments. Sequences were aligned using ClustalW via the EBI website, manually edited using JalView, and used for phylogenetic analyses. In the case of the integrin α alignment, the output from ClustalW consisted of 2383 positions and was manually edited to 1091 positions (20 sequences). The corresponding figures for the integrin β alignments were 2159 positions prior to editing and 991 after editing (24 sequences).
ML analyses of the integrin β sequences (Fig. 5B) confirmed the possible orthology of Podocoryne IntB with the novel Acropora β sequence (AmItgβ2) reported here. Preliminary surveys of the genome sequence of Nematostella suggest the presence of at least four β integrins, and gene models (the gene as predicted in the genome assembly, including the open reading frame, introns and untranslated regions) of these were sufficiently complete for them to be included in phylogenetic analyses (Fig. 5B) which group the Nematostella β integrins with the Acropora subunits – two with AmItgβ1 and two with AmItgβ2. It remains to be seen whether each member of these pairs of Nematostella genes has an Acropora ortholog. As in the integrin α phylogeny, the sponge sequences were relatively distant to those from the Cnidaria. Again, the analyses were broadly consistent with previous studies [20–22], resolving the vertebrate sequences into three clades known as β1 (integrin β1/2/7), β3 (integrin β3/5/6/8) and β4 in the Hughes  phylogeny. Unlike the α integrins, there is no evidence for divergence of β subunits prior to the protostome/deuterostome split. Rather, it appears more likely that β integrins have diverged independently in several bilaterian lineages.
Expression of integrins during coral gastrulation
Whereas Reber-Muller et al.  hypothesized the presence of only single α and β integrin subunits in cnidarians, the integrins identified to date in Acropora are likely to be only a subset of those present. Preliminary surveys of the genome of Nematostella imply that at least four β integrins (two resembling AmItgβ1 and two more similar to AmItgβ2), and at least three distinct α types are present (data not shown). However, gene models for only one α integrin were sufficiently complete to allow its inclusion in the phylogenetic analyses shown as Fig 5A. The integrin repertoire of this morphologically simple animal is therefore considerably more complex than that of Caenorhabditis (one β and two αs), which has often been assumed to reflect the ancestral metazoan state.
Due to structural constraints on integrin proteins during evolution, phylogenetic analyses are likely to be complicated by homoplasy effects. The position of the cnidarian sequences in the α integrin phylogeny (Fig. 5A) is likely due to both the early divergence of the Cnidaria and homoplasy effects. Hence, in this case, phylogenetics is not informative as to ligand binding properties. It is likely that in cnidarians, as in higher animals, distinct α integrin types participate in binding to laminin and RGD-containing ligands, but functional analyses are required to verify this hypothesis.
Despite having a common pattern of cysteine loss, phylogenetic analyses (Fig 5B) indicate that AmItgβ2 is only distantly related to the vertebrate β4-type. Those cysteine residues (positions 8 and 9) in the consensus absent from the Acropora and Podocoryne sequences form the c8–c9 loop of the β A domain, which has been implicated in determining integrin-ligand specificity, specificity of α-β interactions, and signalling properties [24–28]. Whilst this loss has apparently occurred independently of that leading to the vertebrate β4 type, it may result in common consequences for ligand and/or α-subunit specificity.
The presence of maternal integrin mRNAs and their relatively uniform expression through development reported here for Acropora have precedents in Podocoryne  as well as in higher animals. Co-localization of mRNAs for AmItgβ1, AmItgβ2 and AmItgα1 suggests that either or both of the β subunits associate with the α1 subunit. There are many precedents from bilaterians for RGD-type αs associating with β1-type βs (α5β1; αVβ1; α8β1; PS2βPS). Of these, α5β1 and PS2βPS have been implicated as regulators of gastrulation in vertebrates [29, 30] and Drosophila  respectively. In Podocoryne, IntA is assumed to associate with IntB (a possible AmItgβ2 ortholog) since they are co-expressed in a wide variety of locations over a range of life cycle stages , suggesting that AmItgβ2 may associate with the AmItgα1 subunit.
Although integrins clearly play important roles in gastrulation in several animal groups, including vertebrates , Drosophila , and sea urchins , the interactions that have been demonstrated are heterogeneous with respect to both the ligands and types of integrins involved. The expression patterns of α and β integrin genes observed in the coral are reminiscent of expression during both amphibian and sea urchin gastrulation. Modulation of integrin adhesion to the RGD domain of fibronectin plays a central role during Xenopus gastrulation , and in the sea urchin Lytechinus changes in laminin adhesion mediated by the epithelial α integrin α SU2 are likewise important . In both the sea urchin and Xenopus, changes in integrin-mediated cell adhesion during gastrulation occur independently of transcription and translation. In Acropora, integrin mRNAs are present in eggs  and the extent to which those visualized in the presumptive endoderm reflect zygotic transcription is unknown.
The simplest interpretation of the patterns of integrin expression is that they reflect increases in cell adhesion in the presumptive endoderm. Expression on the concave side of the "fat prawn chip" stage embryo, which is essentially a flat bilayer of cells (for a description of gastrulation in Acropora, see ), suggests that integrin-based adhesion may constrain the presumptive endoderm whilst the cells of the presumptive ectoderm move upward and inward around them. Whilst the cells that will end up inside the embryo may adhere to each other more tightly than they do to the putative ectoderm, as is consistent with many forms of gastrulation, the inferred increased adhesion in the putative endoderm is not consistent with a typical epithelial to mesenchymal transition.
The early expression patterns of the α and β integrins in Acropora are very similar to those of two transcription factors, snailA  and otxB . Snail genes have central and conserved roles in gastrulation in Drosophila  and vertebrates  and members of the broader class of related genes are regulators of other epithelial to mesenchymal transitions (EMTs). Whilst the best understood means by which snail genes regulate cell adhesion is by acting as repressors of E-cadherin expression [36, 38, 39], in human epidermal keratinocytes the snail-related gene Slug (Snail2) is a repressor of α3, β1 and β4 integrin expression, leading to decreased cell-adhesion to fibronectin and laminin 5 . Across the Bilateria, Otx genes are conserved anterior markers  and, whilst most Otx genes are expressed in the nervous system, evidence from a diverse range of metazoans suggests an ancient role as regulators of cell adhesion (eg. [42, 43]). In Hydra, high levels of CnOtx expression correspond to regions where cells are undergoing rearrangements or movement . Both snailA and otxB are thus candidate regulators of integrin expression in Acropora. Given the similarity of AmItgα1 to diverged RGD-type mammalian integrins, it will be of particular interest to examine the expression of ECM proteins containing fibronectin type III domains during cnidarian gastrulation in parallel with adhesion studies. Candidates identified in Nematostella include predicted proteins similar to vertebrate usherin and titin, and a likely homolog of Drosophila sidekick.
Whilst one might expect morphologically simple metazoans to have a correspondingly basic integrin complement, comprising perhaps just two αs and a single β subunit (as in Caenorhabditis elegans), the repertoire of these molecules in anthozoan cnidarians is considerably more complex. In the case of cnidarian α integrins, ligand specificity cannot be predicted by phylogenetic analysis, suggesting the possibility that specificity mechanisms arose independently in Cnidaria and Bilateria. During early development in Acropora, some of these adhesion/signalling molecules are expressed in patterns which parallel those of their amphibian and echinoderm counterparts, and which are inconsistent with gastrulation being a simple epithelial to mesenchymal transition.
Sample collection and RNA extraction
Developmentally staged Acropora millepora embryos were collected during annual spawning events. Embryos were staged based on Ball et al. (2002). Total RNA was extracted using RNAWIZ (Ambion) according to the manufacturer's protocol.
RNA was treated with DNase (Fermentas) to remove contaminating genomic DNA. Single stranded cDNA was synthesised using the First-strand cDNA Synthesis Kit (Amersham Biosciences, Piscataway, NJ) using 1 μg of total RNA. One μl of this product was used as a polymerase chain reaction (PCR) template. For AmItgα1, primers AmItga1RTF (5'-GCCAATGAAACAGCTACG-3') and AmItga1RTR (5'-TTGTCTCCAGCCTTCAAC-3') were used to amplify a 130 bp product. For AmItgβ2, primers AmItgb2RTF (5'-TGGGCATTTGTGGTGTGAG-3') and AmItgb2RTR (5'-GCTTGTTCTGATGAGTGATGG-3') were used to amplify a 219 bp product. For AmItgβ1 (Brower et al. 1997), primers IB1RTF (5'-CTTGTGTTGCCACTTATGGCTT-3') and IB1RTR (5'-CTGCTACTTGCATTAACGCATC-3') were used to amplify a 144 bp product. The PCR protocol was 1 min at 94°C, then 40 cycles of 0.5 min at 94°C (denaturation), 0.5 min at 50°C (annealing), 2 min at 72°C (extension), followed by an additional extension for 2 min at 72°C.) As a control, primers ADH-F (5'-AAGAAGACAAACATCAAGCCTCA-3') and ADH-R (5'-CACATCCAAGGTTCACAAGACG-3') were used to amplify a portion of coral AdoHcyase (S-adenosyl-L-homocysteine hydrolase) cDNA (unpublished data).
Whole mount in situ hybridization
The basic procedures for fixation and hybridization with coral embryos were carried out as described . Photographs were captured directly with a Spot digital camera. Digitised images were processed with Adobe Photoshop.
The authors thank the late Danny Brower for advice and critical input. This work was supported by grants from the Australian Research Council, both directly to DJM and EEB and via the Centre of Excellence for Coral Reef Studies and the Special Research Centre for the Molecular Genetics of Development. BAK acknowledges a James Cook University Postgraduate Research Scholarship, and AI and CS were supported by scholarships from the Okinawa International Exchange and Human Resources Development Council.
- Hynes RO: Integrins: bidirectional, allosteric signaling machines. Cell. 2002, 110: 673-687. 10.1016/S0092-8674(02)00971-6.View ArticlePubMedGoogle Scholar
- De Arcangelis A, Georges-Labouesse E: Integrin and ECM functions: roles in vertebrate development. Trends Genet. 2000, 16: 389-395. 10.1016/S0168-9525(00)02074-6.View ArticlePubMedGoogle Scholar
- Marsden M, DeSimone DW: Integrin-ECM interactions regulate cadherin-dependent cell adhesion and are required for convergent extension in Xenopus. Curr Biol. 2003, 13: 1182-1191. 10.1016/S0960-9822(03)00433-0.View ArticlePubMedGoogle Scholar
- consortium C: Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998, 282: 2012-2018. 10.1126/science.282.5396.2012.View ArticleGoogle Scholar
- Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF, George RA, Lewis SE, Richards S, Ashburner M, Henderson SN, Sutton GG, Wortman JR, Yandell MD, Zhang Q, Chen LX, Brandon RC, Rogers YH, Blazej RG, Champe M, Pfeiffer BD, Wan KH, Doyle C, Baxter EG, Helt G, Nelson CR, Gabor GL, Abril JF, Agbayani A, An HJ, Andrews-Pfannkoch C, Baldwin D, Ballew RM, Basu A, Baxendale J, Bayraktaroglu L, Beasley EM, Beeson KY, Benos PV, Berman BP, Bhandari D, Bolshakov S, Borkova D, Botchan MR, Bouck J, Brokstein P, Brottier P, Burtis KC, Busam DA, Butler H, Cadieu E, Center A, Chandra I, Cherry JM, Cawley S, Dahlke C, Davenport LB, Davies P, de Pablos B, Delcher A, Deng Z, Mays AD, Dew I, Dietz SM, Dodson K, Doup LE, Downes M, Dugan-Rocha S, Dunkov BC, Dunn P, Durbin KJ, Evangelista CC, Ferraz C, Ferriera S, Fleischmann W, Fosler C, Gabrielian AE, Garg NS, Gelbart WM, Glasser K, Glodek A, Gong F, Gorrell JH, Gu Z, Guan P, Harris M, Harris NL, Harvey D, Heiman TJ, Hernandez JR, Houck J, Hostin D, Houston KA, Howland TJ, Wei MH, Ibegwam C, Jalali M, Kalush F, Karpen GH, Ke Z, Kennison JA, Ketchum KA, Kimmel BE, Kodira CD, Kraft C, Kravitz S, Kulp D, Lai Z, Lasko P, Lei Y, Levitsky AA, Li J, Li Z, Liang Y, Lin X, Liu X, Mattei B, McIntosh TC, McLeod MP, McPherson D, Merkulov G, Milshina NV, Mobarry C, Morris J, Moshrefi A, Mount SM, Moy M, Murphy B, Murphy L, Muzny DM, Nelson DL, Nelson DR, Nelson KA, Nixon K, Nusskern DR, Pacleb JM, Palazzolo M, Pittman GS, Pan S, Pollard J, Puri V, Reese MG, Reinert K, Remington K, Saunders RD, Scheeler F, Shen H, Shue BC, Siden-Kiamos I, Simpson M, Skupski MP, Smith T, Spier E, Spradling AC, Stapleton M, Strong R, Sun E, Svirskas R, Tector C, Turner R, Venter E, Wang AH, Wang X, Wang ZY, Wassarman DA, Weinstock GM, Weissenbach J, Williams SM, WoodageT, Worley KC, Wu D, Yang S, Yao QA, Ye J, Yeh RF, Zaveri JS, Zhan M, Zhang G, Zhao Q, Zheng L, Zheng XH, Zhong FN, Zhong W, Zhou X, Zhu S, Zhu X, Smith HO, Gibbs RA, Myers EW, Rubin GM, Venter JC: The genome sequence of Drosophila melanogaster. Science. 2000, 287: 2185-2195. 10.1126/science.287.5461.2185.View ArticlePubMedGoogle Scholar
- Whittaker CA, Hynes RO: Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere. Mol Biol Cell. 2002, 13: 3369-3387. 10.1091/mbc.E02-05-0259.PubMed CentralView ArticlePubMedGoogle Scholar
- Brower DL, Brower SM, Hayward DC, Ball EE: Molecular evolution of integrins: genes encoding integrin beta subunits from a coral and a sponge. Proc Natl Acad Sci U S A. 1997, 94: 9182-9187. 10.1073/pnas.94.17.9182.PubMed CentralView ArticlePubMedGoogle Scholar
- Pancer Z, Kruse M, Muller I, Muller WE: On the origin of Metazoan adhesion receptors: cloning of integrin alpha subunit from the sponge Geodia cydonium. Mol Biol Evol. 1997, 14: 391-398.View ArticlePubMedGoogle Scholar
- Wimmer W, Perovic S, Kruse M, Schroder HC, Krasko A, Batel R, Muller WE: Origin of the integrin-mediated signal transduction. Functional studies with cell cultures from the sponge Suberites domuncula. Eur J Biochem. 1999, 260: 156-165. 10.1046/j.1432-1327.1999.00146.x.View ArticlePubMedGoogle Scholar
- Muller WE: Origin of metazoan adhesion molecules and adhesion receptors as deduced from cDNA analyses in the marine sponge Geodia cydonium: a review. Cell Tissue Res. 1997, 289: 383-395. 10.1007/s004410050885.View ArticlePubMedGoogle Scholar
- Reber-Muller S, Studer R, Muller P, Yanze N, Schmid V: Integrin and talin in the jellyfish Podocoryne carnea. Cell Biol Int. 2001, 25: 753-769. 10.1006/cbir.2000.0708.View ArticlePubMedGoogle Scholar
- Ball EE, Hayward DC, Saint R, Miller DJ: A simple plan--cnidarians and the origins of developmental mechanisms. Nat Rev Genet. 2004, 5: 567-577. 10.1038/nrg1402.View ArticlePubMedGoogle Scholar
- Technau U, Rudd S, Maxwell P, Gordon PM, Saina M, Grasso LC, Hayward DC, Sensen CW, Saint R, Holstein TW, Ball EE, Miller DJ: Maintenance of ancestral complexity and non-metazoan genes in two basal cnidarians. Trends Genet. 2005, 21: 633-639. 10.1016/j.tig.2005.09.007.View ArticlePubMedGoogle Scholar
- Hayward DC, Samuel G, Pontynen PC, Catmull J, Saint R, Miller DJ, Ball EE: Localized expression of a dpp/BMP2/4 ortholog in a coral embryo. Proc Natl Acad Sci U S A. 2002, 99: 8106-8111. 10.1073/pnas.112021499.PubMed CentralView ArticlePubMedGoogle Scholar
- Hayward DC, Miller DJ, Ball EE: snail expression during embryonic development of the coral Acropora: blurring the diploblast/triploblast divide?. Dev Genes Evol. 2004, 214: 257-260. 10.1007/s00427-004-0398-0.View ArticlePubMedGoogle Scholar
- Kortschak RD, Samuel G, Saint R, Miller DJ: EST analysis of the cnidarian Acropora millepora reveals extensive gene loss and rapid sequence divergence in the model invertebrates. Curr Biol. 2003, 13: 2190-2195. 10.1016/j.cub.2003.11.030.View ArticlePubMedGoogle Scholar
- Tozer EC, Hughes PE, Loftus JC: Ligand binding and affinity modulation of integrins. Biochem Cell Biol. 1996, 74: 785-798.View ArticlePubMedGoogle Scholar
- Tuckwell DS, Brass A, Humphries MJ: Homology modelling of integrin EF-hands. Evidence for widespread use of a conserved cation-binding site. Biochem J. 1992, 285 ( Pt 1): 325-331.View ArticleGoogle Scholar
- Adachi J, Hasegawa M: Instability of quartet analyses of molecular sequence data by the maximum likelihood method: the Cetacea/Artiodactyla relationships. Mol Phylogenet Evol. 1996, 6: 72-76. 10.1006/mpev.1996.0059.View ArticlePubMedGoogle Scholar
- Hughes AL: Evolution of the integrin alpha and beta protein families. J Mol Evol. 2001, 52: 63-72.View ArticlePubMedGoogle Scholar
- Ewan R, Huxley-Jones J, Mould AP, Humphries MJ, Robertson DL, Boot-Handford RP: The integrins of the urochordate Ciona intestinalis provide novel insights into the molecular evolution of the vertebrate integrin family. BMC Evol Biol. 2005, 5: 31-10.1186/1471-2148-5-31.PubMed CentralView ArticlePubMedGoogle Scholar
- Huhtala M, Heino J, Casciari D, de Luise A, Johnson MS: Integrin evolution: insights from ascidian and teleost fish genomes. Matrix Biol. 2005, 24: 83-95. 10.1016/j.matbio.2005.01.003.View ArticlePubMedGoogle Scholar
- Iguchi A, Marquez LM, Knack B, Shinzato C, van Oppen MJ, Willis BL, Hardie K, Catmull J, Miller DJ: Apparent Involvement of a beta1 Type Integrin in Coral Fertilization. Mar Biotechnol (NY). 2007Google Scholar
- Bunch TA, Miller SW, Brower DL: Analysis of the Drosophila betaPS subunit indicates that regulation of integrin activity is a primal function of the C8-C9 loop. Exp Cell Res. 2004, 294: 118-129. 10.1016/j.yexcr.2003.11.002.View ArticlePubMedGoogle Scholar
- Takagi J, Kamata T, Meredith J, Puzon-McLaughlin W, Takada Y: Changing ligand specificities of alphavbeta1 and alphavbeta3 integrins by swapping a short diverse sequence of the beta subunit. J Biol Chem. 1997, 272: 19794-19800. 10.1074/jbc.272.32.19794.View ArticlePubMedGoogle Scholar
- Lin CS, Chen Y, Huynh T, Kramer R: Identification of the human alpha6 integrin gene promoter. DNA Cell Biol. 1997, 16: 929-937.View ArticlePubMedGoogle Scholar
- Takagi J, DeBottis DP, Erickson HP, Springer TA: The role of the specificity-determining loop of the integrin beta subunit I-like domain in autonomous expression, association with the alpha subunit, and ligand binding. Biochemistry. 2002, 41: 4339-4347. 10.1021/bi016047u.View ArticlePubMedGoogle Scholar
- Miao H, Li S, Hu YL, Yuan S, Zhao Y, Chen BP, Puzon-McLaughlin W, Tarui T, Shyy JY, Takada Y, Usami S, Chien S: Differential regulation of Rho GTPases by beta1 and beta3 integrins: the role of an extracellular domain of integrin in intracellular signaling. J Cell Sci. 2002, 115: 2199-2206.PubMedGoogle Scholar
- Davidson LA, Hoffstrom BG, Keller R, DeSimone DW: Mesendoderm extension and mantle closure in Xenopus laevis gastrulation: combined roles for integrin alpha(5)beta(1), fibronectin, and tissue geometry. Dev Biol. 2002, 242: 109-129. 10.1006/dbio.2002.0537.View ArticlePubMedGoogle Scholar
- Whittaker CA, DeSimone DW: Integrin alpha subunit mRNAs are differentially expressed in early Xenopus embryos. Development. 1993, 117: 1239-1249.PubMedGoogle Scholar
- Roote CE, Zusman S: Functions for PS integrins in tissue adhesion, migration, and shape changes during early embryonic development in Drosophila. Dev Biol. 1995, 169: 322-336. 10.1006/dbio.1995.1147.View ArticlePubMedGoogle Scholar
- Marsden M, Burke RD: The betaL integrin subunit is necessary for gastrulation in sea urchin embryos. Dev Biol. 1998, 203: 134-148. 10.1006/dbio.1998.9033.View ArticlePubMedGoogle Scholar
- Ramos JW, DeSimone DW: Xenopus embryonic cell adhesion to fibronectin: position-specific activation of RGD/synergy site-dependent migratory behavior at gastrulation. J Cell Biol. 1996, 134: 227-240. 10.1083/jcb.134.1.227.View ArticlePubMedGoogle Scholar
- Hertzler PL, McClay DR: alphaSU2, an epithelial integrin that binds laminin in the sea urchin embryo. Dev Biol. 1999, 207: 1-13. 10.1006/dbio.1998.9165.View ArticlePubMedGoogle Scholar
- de Jong DM, Hislop NR, Hayward DC, Reece-Hoyes JS, Pontynen PC, Ball EE, Miller DJ: Components of both major axial patterning systems of the Bilateria are differentially expressed along the primary axis of a 'radiate' animal, the anthozoan cnidarian Acropora millepora. Dev Biol. 2006, 298: 632-643. 10.1016/j.ydbio.2006.07.034.View ArticlePubMedGoogle Scholar
- Ip YT, Gridley T: Cell movements during gastrulation: snail dependent and independent pathways. Curr Opin Genet Dev. 2002, 12: 423-429. 10.1016/S0959-437X(02)00320-9.View ArticlePubMedGoogle Scholar
- Carver EA, Jiang R, Lan Y, Oram KF, Gridley T: The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol Cell Biol. 2001, 21: 8184-8188. 10.1128/MCB.21.23.8184-8188.2001.PubMed CentralView ArticlePubMedGoogle Scholar
- Barrallo-Gimeno A, Nieto MA: The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development. 2005, 132: 3151-3161. 10.1242/dev.01907.View ArticlePubMedGoogle Scholar
- Nieto MA: The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol. 2002, 3: 155-166. 10.1038/nrm757.View ArticlePubMedGoogle Scholar
- Turner FE, Broad S, Khanim FL, Jeanes A, Talma S, Hughes S, Tselepis C, Hotchin NA: Slug regulates integrin expression and cell proliferation in human epidermal keratinocytes. J Biol Chem. 2006, 281: 21321-21331. 10.1074/jbc.M509731200.View ArticlePubMedGoogle Scholar
- Lichtneckert R, Reichert H: Insights into the urbilaterian brain: conserved genetic patterning mechanisms in insect and vertebrate brain development. Heredity. 2005, 94: 465-477. 10.1038/sj.hdy.6800664.View ArticlePubMedGoogle Scholar
- Bellipanni G, Murakami T, Doerre OG, Andermann P, Weinberg ES: Expression of Otx homeodomain proteins induces cell aggregation in developing zebrafish embryos. Dev Biol. 2000, 223: 339-353. 10.1006/dbio.2000.9771.View ArticlePubMedGoogle Scholar
- Perea-Gomez A, Lawson KA, Rhinn M, Zakin L, Brulet P, Mazan S, Ang SL: Otx2 is required for visceral endoderm movement and for the restriction of posterior signals in the epiblast of the mouse embryo. Development. 2001, 128: 753-765.PubMedGoogle Scholar
- Smith KM, Gee L, Blitz IL, Bode HR: CnOtx, a member of the Otx gene family, has a role in cell movement in hydra. Dev Biol. 1999, 212: 392-404. 10.1006/dbio.1999.9337.View ArticlePubMedGoogle Scholar
- Hayward DC, Catmull J, Reece-Hoyes JS, Berghammer H, Dodd H, Hann SJ, Miller DJ, Ball EE: Gene structure and larval expression of cnox-2Am from the coral Acropora millepora. Dev Genes Evol. 2001, 211: 10-19. 10.1007/s004270000112.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.